title: A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium.
abstract: OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.
authors.affiliation: Division of Statistical Genomics, Washington University School of Medicine, Saint Louis, Missouri, USA. aldi@wustl.edu
authors.forename: Aldi T
authors.initials: AT
authors.lastname: Kraja
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mary F
authors.initials: MF
authors.lastname: Feitosa
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Knowles
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Carlos
authors.initials: C
authors.lastname: Iribarren
authors.forename: Brian
authors.initials: B
authors.lastname: Kral
authors.forename: Lisa
authors.initials: L
authors.lastname: Yanek
authors.forename: Paul F
authors.initials: PF
authors.lastname: O'Reilly
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Cashell
authors.initials: C
authors.lastname: Jaquish
authors.forename: David J
authors.initials: DJ
authors.lastname: Couper
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.forename: Leena
authors.initials: L
authors.lastname: Palotie
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics